Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice
Ssebyatika G, Dinkelborg K, Ströh L, Hinte F, Corneillie L, Hueffner L, Guzman E, Nankya P, Plückebaum N, Fehlau L, Garn J, Meyer N, Prallet S, Mehnert A, Kraft A, Verhoye L, Jacobsen C, Steinmann E, Wedemeyer H, Viejo-Borbolla A, Dao Thi V, Pietschmann T, Lütgehetmann M, Meuleman P, Dandri M, Krey T, Behrendt P
Published in
Nature communications: Volume 16, Issue 1, Page 1995
Abstract
Hepatitis E virus (HEV) causes 3.3 million symptomatic cases and 44,000 deaths per year. Chronic infections can arise in immunocompromised individuals, and pregnant women may suffer from fulminant disease as a consequence of HEV infection. Despite these important implications for public health, no specific antiviral treatment has been approved to date. Here, we report combined functional, biochemical, and X-ray crystallographic studies that characterize the human antibody response in convalescent HEV patients. We identified a class of potent and broadly neutralizing human antibodies (bnAbs), targeting a quaternary epitope located at the tip of the HEV capsid protein pORF2 that contains an N-glycosylation motif and is conserved across members of the Hepeviridae. These glycan-sensitive bnAbs specifically recognize the non-glycosylated pORF2 present in infectious particles but not the secreted glycosylated form acting as antibody decoy. Our most potent bnAb protects human liver-chimeric mice from intraperitoneal HEV challenge and co-housing exposure. These results provide insights into the bnAb response to this important emerging pathogen and support the development of glycan-sensitive antibodies to combat HEV infection.
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